Biomedical subjects

M Miozzo

Publications and source records attributed to M Miozzo.

At least 19 recordsLinked to original sources

PubMed2005

Fetal and placental chromosomal mosaicism revealed by QF-PCR in severe IUGR pregnancies.

A number of genetic and environmental factors are taken into account as responsible for intrauterine growth restriction (IUGR); nevertheless, the relevance of genetic alteration in IUGR aetiology remains to be determined. The aim of this study was to investigate using a combined cytogenetic-molecular approach, improved by a new application of QF-PCR method, the presence of mosaic chromosomal changes in fetal/placental samples from 12 pregnancies with unexplained severe IUGR. This multiple approach allowed us to reveal and quantify subtle chromosomal mosaicisms with less than 5% of trisomic cells even in cases in which cytogenetic and FISH analyses failed to reveal them. These are three pregnancies with a mosaic trisomy for chromosomes 7, 2 and 14; the former case presented matUPD7 and was previously described in this journal (Placenta 22 (2001) 813) in association with pre- and postnatal growth restriction. It is intriguing that chromosomes 7, 2 and 14 are known or suspected to harbour imprinted genes, so that an unbalanced gene dosage in a subset of cells during embryonic development could lead to an early impairment of placental function. Our findings indicate that extensive molecular and cytogenetic studies of IUGR fetal and placental tissues are necessary to reveal at least part of the heterogeneous genetic lesions implicated in IUGR phenotypes.

Adult↗

PubMed2001

A patient defines the interstitial 1q deletion syndrome characterized by antithrombin III deficiency.

A patient with microbrachycephaly, high forehead, long philtrum, thin upper lip, downturned corners of the mouth, low set ears with overlapping helix, fifth-finger clinodactyly, small hands and feet, bilateral transverse palmar crease, low total finger ridge count, hypotonia, severe growth and psychomotor delay, mild hypoplasia of corpus callosum, and Arnold-Chiari type 1 malformation is reported. The karyotype showed 46, XY, del(1)(q23q31.2). Coagulation factor V (F5, 1q23) and coagulation factor XIII (F13B, 1q31-q32.1) levels were normal. As expected, antithrombin III (AT3, 1q23-q25.1) serum level and activity were half of normal. We performed a review of the literature on proximal and intermediate deletion 1q syndrome, and we hypothesize the existence of only one 1q interstitial deletion syndrome, clinically characterized by ATIII deficiency.

Adolescent↗

PubMed2001

Relationship between clinical and genetic features in "inverted duplicated chromosome 15" patients.

Inverted duplicated chromosome 15 (Inv dup [15]) syndrome is a genetic disorder characterized by psychologic or intellectual language delay; neurologic signs, such as hypotonia, ataxia, and epilepsy; mental retardation ranging from mild to severe; and facial dysmorphisms. All patients present with a psychopathologic impairment that is highly variable in severity but always classifiable as pervasive developmental disorder (PDD). Many genetic mechanisms have been hypothesized to explain the clinical variability. This article describes the neurologic and psychopathologic features of six Inv dup(15) patients, one male and five females, between 8 and 14 years of age, all with a maternal marker chromosome. Four patients were diagnosed with PDD not otherwise specified, whereas two patients received a diagnosis of autism. Epilepsy was present in three patients (two generalized symptomatic and one focal symptomatic), and a correlation between the severity of the disease and its outcome was not always observed. Nevertheless, the influence of gene content of the marker chromosome, particularly the three gamma-aminobutyric acid-A receptor subunit genes, may represent the link between epilepsy, mental retardation, and PDD.

Adolescent↗

PubMed2001

Post-zygotic origin of complete maternal chromosome 7 isodisomy and consequent loss of placental PEG1/MEST expression.

Maternal UPD of chromosome 7 is associated with pre- and postnatal growth retardation (IUGR, PNGR) and Silver-Russell syndrome (SRS [MIM 180860]). We report a case of IUGR in a newborn with SRS stigmata. Using combined haplotyping and cytogenetic-FISH studies we characterized the lymphocytes, umbilical cord and four placental cotyledons. The results are consistent with complete maternal isodisomy 7 and trisomy 7 mosaicism of post-zygotic origin. The trisomic cell line was prevalent in trophoblast cells from two placental cotyledons. Trisomy 7 of post-zygotic origin is a frequent finding, but maternal isodisomy 7, due to trisomic rescue has never been reported. PEG1/MEST expression was evaluated on placenta cDNA and a specific transcript was revealed only in the cotyledons with a high percentage of trisomic cells and the presence of the paternal chromosome 7 contribution, but not in the placental biopsies with maternal isodisomy 7. The histological features of the four placental fragments revealed that isodisomy 7 correlates with a pattern of cotyledonary hyper-ramification due to an increase of the branching angiogenesis, which could be the result of a defect of angiogenesis caused by the absence of PEG1 product. The severe hypo-ramification of the two cotyledons, showing trisomy 7 mosaicism, may be due to the triplicate dosage of genes on chromosome 7. The delayed fetal growth could be the phenotypic effect of the imbalance between imprinted and non-imprinted genes on chromosome 7 in the fetus or the result of abnormal placental function during pregnancy.

Adult↗

PubMed2001

The specific-word frequency effect: implications for the representation of homophones in speech production.

In a series of experiments, the authors investigated whether naming latencies for homophones (e.g., /nlambdan/) are a function of specific-word frequency (i.e., the frequency of nun) or a function of cumulative-homophone frequency (i.e., the sum of the frequencies of nun and none). Specific-word but not cumulative-homophone frequency affected picture-naming latencies. This result was obtained in 2 languages (English and Chinese). An analogous finding was obtained in a translation task, where bilingual speakers produced the English names of visually presented Spanish words. Control experiments ruled out that these results are an artifact of orthographic or articulatory factors, or of visual recognition. The results argue against the hypothesis that homophones share a common word-form representation, and support instead a model in which homophones have fully independent representations.

Adult↗

PubMed2000

Patient with large 17p11.2 deletion presenting with Smith-Magenis syndrome and Joubert syndrome phenotype.

We report on a 22-year-old woman carrying a del(17)(p11.2p12) and presenting with the clinical manifestations of both Smith-Magenis syndrome (SMS) and Joubert syndrome (JS). Her facial anomalies, brachydactyly, severe mental retardation, and self-injuring behavior could be attributed to SMS, whereas the cerebellar vermis hypoplasia, hypotonia, ataxic gait, developmental delay, and abnormal respiratory pattern were suggestive of JS. By fluorescent in situ hybridization analyses with Yeast Artificial Chromosomes (YAC) mapping to the 17p11.2 region, as well as locus-specific probes generated through a novel procedure, we could establish that the deletion encompasses a 4-Mb interval with centromeric and telomeric breakpoints at loci D17S793 and D17S953, the latter close to the locus Charcot Marie Tooth 1A (CMT1A)-REP. The deletion differs from that commonly found in SMS in its telomeric boundary, which is more distal than usually observed. The presence of JS phenotype in our patient and the detection of an unusual SMS deletion might suggest the presence of a JS gene in close proximity to the SMS locus.

Abnormalities, Multiple↗

PubMed2000

A tumor suppressor locus in familial and sporadic chordoma maps to 1p36.

Previous cytogenetic/FISH data have demonstrated 1p36 deletions in a relapsing familial clivus chordoma developed by a patient who has 2 daughters, respectively affected with childhood astrocytoma and clivus chordoma. Using an approach that combined the LOH (loss of heterozygosity) study of the father chordoma and the daughter astrocytoma and a segregation analysis from parents to sibs using 17 CA-repeats spanning 1p36.32-1p36.11, we mapped the cancer susceptibility locus in this family to the 1p36 region. The LOH and haplotype information was elaborated using a pairwise linkage analysis that gave a maximum lod score of 1.2. Additional LOH data relating to 6 sporadic chordomas allowed us to define an SRO (the smallest region of overlapping loss) of about 25 cM from D1S2845 (1p36.31) to D1S2728 (1p36.13). Our overall findings converge on mapping to 1p36 a tumor-suppressor gene involved in familial and sporadic chordoma.

Adult↗

PubMed2000

19p deletion in recurring leiomyosarcoma lesions from the same patient.

Ten leiomyosarcomas (LMS) affecting the same patient over a period of 3 years were cytogenetically studied to detect nonrandom chromosomal changes with a pathogenetic significance. All tumors, likely metastases of a previous LMS presentation, were classified as small, including eight that developed before chemotherapy; the diagnoses were based on standard immunohistochemistry methods for smooth muscle tumors. Scoring of 613 metaphases revealed monosomy of chromosome 22 in six LMS, monosomy of chromosome 19 in three, and deletion of chromosome 19p in all ten. Interphase fluorescence in situ hybridization (FISH) of the 22-alphoid-specific probe allowed loss of the target chromosome to be detected in four tumors at higher frequencies than those detected by cytogenetics. Double-color FISH of the 19p- and 19q-specific YAC performed on one tumor made it possible to distinguish the monosomic and 19p deleted cells, the relative frequencies of which were found to be 10% and 20%, respectively. The deletion breakpoint could be mapped at 19p13 between YAC 957d12 and YAC 947g4. The recurrence of the 19p deletion in a subset of tumor cells from all of the analyzed LMS suggests that this structural aberration is a significant change in the development of leiomyosarcomas.

Adult↗

PubMed1999

First cytogenetic study of a recurrent familial chordoma of the clivus.

Two recurrences of a familial clivus chordoma, arisen from a patient who developed the primary tumor at age of 8 years, were investigated by cytogenetic and the fluorescence in situ hybridization (FISH) approach. Of the patient's 3 daughters, 2 developed, respectively, a clivus chordoma and an astrocytoma in infancy, a familial aggregation highly suggestive of a genetic background. After a 31-year hiatus, 2 tumor recurrences, developed over 17 months, were removed surgically. Both were hypo- or nearly diploid, and had a pronounced karyotypic heterogeneity with clonal and non-clonal rearrangements affecting several chromosomes. The same rearrangement, a dic(1;9)(p36.1;p21), was shared in both tumor specimens and, in 90% of the cells, chromosome 1p appeared to be involved in unbalanced translocations with different chromosomes, leading to variable losses of 1p. Previous cytogenetic data concerning chordoma are limited to 10 sporadic tumors with an abnormal karyotype; although no tumor-specific rearrangements have been identified, chromosome 1p appears to be involved frequently.

Adolescent↗

PubMed1999

The selection of determiners in noun phrase production.

Picture-word interference experiments conducted with Italian speakers investigated how determiners are selected in noun phrase (NP) production. Determiner production involves the selection of a noun's syntactic features (mass or count, gender), which specify the type of determiner to be selected, and the subsequent selection of a particular phonological form (e.g., the/a in English). The research focused on the syntactic feature of gender. Results repeatedly failed to replicate the gender-congruity effect in NP production reported with Dutch speakers (longer latencies for target-distractor noun pairs with contrasting as opposed to the same gender). It is proposed that the discrepant results reflect processing differences in lexical access in Italian and Dutch: The selection of determiners in Italian, but not in Dutch, depends on phonological properties of the word that follows it in the NP. Evidence consistent with this explanation was obtained in an experiment in which determiner selection in NP production was hindered by conflicting phonological information in the NP.

Adult↗

PubMed1998

Chromosomal instability in fibroblasts and mesenchymal tumors from 2 sibs with Rothmund-Thomson syndrome.

Rothmund-Thomson syndrome (RTS) is a rare autosomal recessive genodermatosis associated with increased risk of mesenchymal tumors. The putative gene has been provisionally assigned to chromosome 8. Using a cytogenetic-molecular approach, we studied lymphocytes, fibroblasts, osteosarcoma (OS) and malignant fibrous histiocytoma (MFH) from 2 affected fraternal twins, looking for constitutive markers of chromosome instability and tumor chromosomal changes which might reflect the common genetic background. The rate of spontaneous chromosome aberrations was not increased in lymphocytes. Conversely, karyotyping of primary fibroblasts from one sib evidenced chromosome breaks and both numerical and structural chromosome changes in 24% and 17% of the metaphases respectively. FISH of a 8q21.3 cosmid allowed us to detect trisomy of the target region on 7% of fibroblast nuclei from both sibs, 47% and 12% of OS and MFH cells. Pronounced chromosomal instability and clonal rearrangements leading to different chromosome-8 derivatives were detected in both tumors. CGH experiments showed multiple gains/losses, among which del(6q), also revealed by cytogenetics, and 7p gain were common, whereas 8q amplification was present only in OS. Chromosomal instability, observed in fibroblasts from the RTS patients studied, accounts for the increased risk of mesenchymal tumors in these patients.

Adolescent↗

PubMed1998

More is not always better: a response to Roelofs, Meyer, and Levelt.

In a series of papers we have argued that the distinction between lemma and lexeme levels of representation in lexical access may be unnecessary. We pointed out that the evidence cited in support of this view is not incompatible with alternative accounts that do not assume a lemma level of representation. Furthermore, we argued that there are neuropsychological observations and results from tip-of-the-tongue (TOT) experiments that appear to be problematic for the lemma/lexeme distinction. Roelofs et al. [Roelofs, A., Meyer, A.S., Levelt, W.J.M., 1998. A case for the lemma/lexeme distinction in models of speaking: comment on Caramazza and Miozzo (1997). Cognition 69, 219-230.] have challenged our conclusions by attempting to demonstrate that (1) a model that incorporates the lemma/lexeme distinction can account for the putatively problematic neuropsychological and TOT data; (2) there are other data that appear to be problematic for a type of model that does not include a lemma level of representation. In the present paper we respond to these criticisms by showing (1) that the neuropsychological and TOT data still represent a challenge for the lemma/lexeme distinction, and (2) that the other evidence cited by Roelofs et al. is not incompatible with lexical theories that assume only one lexical layer.

Humans↗

PubMed1997

The relation between syntactic and phonological knowledge in lexical access: evidence from the 'tip-of-the-tongue' phenomenon.

The relation between access to the syntactic and to the phonological features of words in lexical access is investigated in two experiments. Italian speakers were asked to provide the gender and partial phonological information of known nouns they could not produce at that moment, words that they felt were at the tip-of-the-tongue (TOT). In both experiments, subjects were able to provide information about the word they could not produce with better-than-chance accuracy. This was true not only for phonological information such as the initial phoneme of the word but also for the word's gender--a purely syntactic feature of nouns. However, analyses of the correlation between correct retrieval of the gender and the initial phoneme failed to reveal a positive relationship. This result is inconsistent with theories of lexical access the interpose two lexical nodes, lemma and lexeme nodes, between a word's semantic and phonological content. A model of lexical access that does not postulate the lemma/lexeme distinction is briefly discussed.

Adult↗

PubMed1997

Relevance of cytogenetic and fluorescent in situ hybridization analyses in the clinical assessment of soft tissue sarcoma.

Soft tissue sarcomas are a heterogeneous group of malignant tumors displaying a wide range of clinical presentations, morphological features, and biological behaviors. These characteristics and the recent development of differentiated treatment regimens for the different types of soft tissue sarcomas call for refined histological classification using additional ancillary approaches such as cytogenetic and molecular genetic analyses. We coupled classical cytogenetics and fluorescent in situ hybridization (FISH) on both metaphases and interphase nuclei to show the feasibility of this approach to characterize tumor type-specific chromosome rearrangements in soft tissue sarcomas of different histotype. In 35 cases analyzed, we detected the presence of specific chromosome rearrangements such as t(X;18) in synovial sarcoma (SS), t(12;16) in myxoid liposarcoma (MLS), t(11;22) in peripheral primitive neuroectodermal tumors (pPNET), t(2;13) in alveolar rhabdomyosarcoma (ARMS) and ring chromosomes in dermatofibrosarcoma protuberans (DFSP). In several cases, the presence of these cytogenetic rearrangements was of help for a differential diagnosis. The FISH analysis using painting probes not only confirmed the cytogenetic results but also allowed the identification of tumor-specific chromosome changes in those cases presenting low mitotic index or with poor quality chromosomes. Moreover, in the absence of analysable metaphases, FISH was successfully performed on interphase nuclei. Taken together, these results indicate both the diagnostic and clinical relevance of a molecular cytogenetic analysis in the study of soft tissue sarcomas.

Biomarkers, Tumor↗

PubMed1997

Retrieval of lexical-syntactic features in tip-of-the-tongue states.

Italian speakers who signaled that they were in a tip-of-the-tongue (TOT) state were asked to recognize the grammatical gender and the initial and the final phonemes of the unavailable word. The proportions of gender and phoneme hits that occurred with "don't know" (DK) responses were adopted as baselines for chance-level performance. Participants were more accurate in recognizing the grammatical gender and the initial but not the final phoneme of target words when they were in TOT than in DK states. The availability of gender in TOT states suggests the independence of syntactic from phonological information in lexical access. However, the retrieval of gender was far from perfect for TOT words, and it was no better than recognition of the initial phoneme. These results are problematic for the notion that the selection of a lemma is synonymous with the retrieval of the word's syntactic features. The implications of these results for the distinction between lemma and lexeme levels of representation in lexical access are discussed.

Humans↗

PubMed1996

Mapping of a putative tumor suppressor locus to proximal 7p in Wilms tumors.

Different findings suggest that alterations of chromosome 7 genes play a role in the development of Wilms tumors. To define the positions of these genes, we have accomplished a combined cytogenetic and molecular study on 11 sporadic Wilms tumors. In one case, where both chromosomes 7 were rearranged, the karyotypic picture was consistent with the presence of a tumor suppressor gene at 7p15. To test this hypothesis, a loss of heterozygosity analysis was performed using microsatellite markers. This revealed a common region of allele losses mapped to the proximal short arm of chromosome 7 and defined the position of the gene(s) involved in Wilms tumors within an interval of approximately 25 cM.

Chromosome Mapping↗

PubMed1996

Microsatellite alterations in bronchial and sputum specimens of lung cancer patients.

Early diagnosis of lung cancer based on conventional screening procedures has been unable thus far to decrease lung cancer mortality. We explored the possibility of using microsatellite instability in the detection and screening of early phases of lung carcinogenesis. We studied tumor, histopathologically normal bronchial mucosa, and cytological specimens of 51 lung cancer patients for the presence of clonal variations at microsatellite polymorphisms. Microsatellite alterations were found in tumor, normal bronchial mucosa and cytological specimens of 25 of 51 (49%) of the patients. The detection of microsatellite alterations in histopathologically normal bronchial specimens and cytological clinical samples with minimal atypia suggests a possible application of this genetic marker in early diagnosis of precancerous lesions and lung cancer.

Adenocarcinoma↗

PubMed1995

Genetic evidence for an independent origin of multiple preneoplastic and neoplastic lung lesions.

Patients with a primary cancer in the lung or in the upper aerodigestive tract have an increased risk of developing synchronous or metachronous second primary lung tumors. This phenomenon has been related to the chronic exposure of the bronchial tree to carcinogens through a so-called "field cancerization" process. This study was designed to investigate at the somatic level the genetic basis of the field cancerization effect in patients having multiple simultaneous neoplastic and preneoplastic lesions of the lung. The pattern of specific genetic changes occurring with high frequency and in early stages of lung carcinogenesis including p53 mutations, deletions of chromosome 3p, and K-ras mutations, was investigated by immunocytochemical, cytogenetic, and molecular approaches in 11 synchronous lesions of five patients with multiple lung cancers. Different genetic lesions were observed in all of the pathological specimens analyzed from each patient. The pattern of these changes was different both in topographically distant or adjacent lesions and in tumors with the same histopathological diagnosis supporting their independent origin. The present data provide further evidence of the clinical relevance of the field cancerization process, and support the use of genetic markers in the differential diagnosis of recurrence or metastasis versus second primaries of the lung.

Adenocarcinoma↗